BOSTON — A research team including Michael McGeachie, PhD, from Brigham and Women's Hospital in Boston, has published a study in the journal Thorax connecting vitamin A and D levels to lung function through epigenetic mechanisms in both children and adults with asthma. The analysis suggested that microRNAs (miRNAs) and DNA methylation partially mediate this relationship.

The study found that higher vitamin A levels were linked to better lung function in adults and children. Higher vitamin A levels correlated with significantly higher forced expiratory volume in 1 second (FEV1), showing a beta coefficient of 2.5 in children and 4.7 in adults. Higher vitamin A levels also correlated with significantly higher forced vital capacity (FVC), with a beta coefficient of 7.6 in children and 3.4 in adults. In children, higher vitamin A levels were associated with a lower FEV1/FVC ratio (beta coefficient of -3.9), while for adults, the relationship between vitamin A and the FEV1/FVC ratio was positive with a beta coefficient of 2.5.

Benefits from vitamin D were observed among adults but did not correlate with lung function measures in children. Among adults with asthma, those with vitamin D levels of at least 30 ng/ml had better lung function than those with lower levels. Vitamin D had significantly positive associations with FEV1 (beta=0.16) and FVC (beta=0.18) among adults. Adults with higher vitamin D levels had less evidence of epigenetic ageing, and lung function was inversely correlated with all age acceleration measures. McGeachie noted that only about half of the child cohort had vitamin D levels measured. "This discrepancy in children may stem from insufficient statistical power to detect trends in vitamin D levels in our childhood cohort," he said.

The researchers assessed serum miRNA profiles, blood DNA methylation, and plasma or serum vitamin A and D levels in two cohorts. One cohort included 1,165 children aged 6-14 years, with an average age of 9.2 years, from the Genetic Epidemiology of Asthma in Costa Rica Study. The other cohort consisted of 1,041 adults with an average age of 58.8 years from the Omic Determinants of Longitudinal Lung Function in Asthma study of the Mass General Brigham Biobank. Reduced methylation of the IRF5 gene with higher vitamin levels was linked to improved lung function in both children and adults.

Editorialist Sze Man Tse, affiliated with the University of Montreal, commented on the study's approach. "Specifically, they examined how vitamin A and D levels influence regulators (miRNA) and markers of epigenetics (DNA methylation) and used mediation analyses to demonstrate that miRNAs and DNA methylation partially mediate the relationship between vitamin levels and lung function," Tse said. "IRF5 is a transcription factor that plays a critical role in regulating airway macrophage differentiation, inducing proinflammatory responses to microbial and viral infections through the production of interferon (IFN)-α and IFN-β, and controlling allergic and eosinophilic airway inflammation." Tse added, "This would also be concordant with the hypothesis that vitamin A and D have different roles across the lifespan (i.e., lung development and growth in childhood vs lung repair and regeneration in adulthood)." The study findings did not make determinations regarding the benefit of supplementation or dietary changes for asthma patients.

McGeachie stated, "To our knowledge, this is the first study to integrate vitamin A and D levels with lung function and epigenetic markers-miRNA expression and DNA methylation-in both children and adults with asthma." He added, "Both vitamins are versatile micronutrients involved in lung development, primarily through regulation of gene expression." "Our findings emphasize that epigenetic mechanisms play a key role in mediating the effects of vitamins on lung function in individuals with asthma, pointing to potential targets for personalised nutrition and therapeutic strategies in asthma care," McGeachie said.

The study's limitations include its inability to determine causality, the relative quantification of plasma vitamin A, the lack of mRNA expression data, and the absence of longitudinal data. "Future work should address these gaps using absolute, repeated measures to clarify vitamin–lung function dynamics over time," McGeachie said. Tse noted, "While these findings open a novel line of investigation linking vitamin D, biological ageing and lung health, there is a need for further studies to clarify causality." "By examining the underlying biological mechanisms, [the researchers have] revealed a nuanced interplay between vitamins A and D, lung function, and their epigenetic mediators," Tse said. "Interestingly, these common miRNAs regulate 248 genes along pathways that are known to modulate lung inflammation and function and thus could be potential therapeutic targets." Tse concluded, "Overall, advancing our understanding of how nutritional exposures impact gene regulation may open new avenues for managing asthma across the lifespan."